Effective medical management and strategies of secondary prevention for coronary artery disease (CAD) have greatly contributed to the dramatic improvement in heart disease mortality rates seen in the United States during the past decade. Myocardial perfusion imaging (MPI) is useful for diagnosing cardiac ischemia and is a powerful tool for risk stratification of patients with CAD. Indeed, patients with a normal MPI have a very good short to intermediate prognosis. Coronary artery calcium scoring (CACS) using multi-slice or electron beam CT assists in the diagnosis of subclinical CAD, potentially allowing risk factor reduction to begin before physiological significant CAD and coronary events develop. Combining CACS during MPI or performing it after MPI to assist in detecting CAD in patients with normal MPI studies is being utilized with increasing frequency. The additional information obtained by CACS allows the detection of many patients with subclinical disease, alters the prognostic advice to them, leads to alteration in prescribed medical treatment and patient lifestyle, and results in improved risk factor profiles. These cardiovascular risk factor modification and lifestyle changes will presumably result in a reduction in mortality and morbidity related to cardiovascular disease. This review discusses the clinical implications in the diagnosis and treatment of CAD when coronary artery calcium scoring is performed in patients who have a normal myocardial perfusion imaging study.